Evidence map›Paper›PMID 36221071›Full record

ArticleMalaria journal2022

Pre-referral intranasal artesunate powder for cerebral malaria: a proof-of-concept study.

Yobouet Ines Kouakou, Aurelien Millet, Elodie Fromentin, Nathalie Hauchard, Gonçalo Farias, Maxime Fieux, Aurelie Coudert, Roukayatou Omorou, Ibrahim Bin Sa'id, Adeline Lavoignat and 3 more

Open access · goldAbstract read
In one paragraph

Article in Malaria journal, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.8field-weighted citation impact, top 27% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed, 4 citations in OpenAlex.

  1. Article
  2. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 8 institutions in 1 country.

Yobouet Ines KouakouUniv Lyon, Malaria Research Unit, SMITh, ICBMS, UMR 5246 CNRS-INSA-CPE-University Lyon1, 69622, Villeurbanne, France.
Aurelien MilletLaboratory of Biochemistry and Pharmacotoxicology, Lyon-Sud Hospital, Hospices civils de Lyon, 69310, Pierre-Bénite, France.
Elodie FromentinUniv Lyon, CCSM, ICBMS, UMR 5246 CNRS-INSA-CPE-University Lyon1, 69622, Villeurbanne, France.
Nathalie HauchardAptar Pharma, Le Vaudreuil, France.
Gonçalo FariasAptar Pharma, Le Vaudreuil, France.
Maxime FieuxHospices Civils de Lyon, Centre Hospitalier Lyon Sud, Service d'ORL, d'otoneurochirurgie et de chirurgie cervico-faciale, 69310, Pierre Bénite, France.
Aurelie CoudertDepartment of Pediatric Otolaryngology-Head & Neck Surgery, Femme Mere Enfant Hospital-Hospices Civils de Lyon, 69008, Lyon, France.
Roukayatou OmorouUniv Lyon, Malaria Research Unit, SMITh, ICBMS, UMR 5246 CNRS-INSA-CPE-University Lyon1, 69622, Villeurbanne, France.
Ibrahim Bin Sa'idUniv Lyon, Malaria Research Unit, SMITh, ICBMS, UMR 5246 CNRS-INSA-CPE-University Lyon1, 69622, Villeurbanne, France.
Adeline LavoignatUniv Lyon, Malaria Research Unit, SMITh, ICBMS, UMR 5246 CNRS-INSA-CPE-University Lyon1, 69622, Villeurbanne, France.
Guillaume BonnotUniv Lyon, Malaria Research Unit, SMITh, ICBMS, UMR 5246 CNRS-INSA-CPE-University Lyon1, 69622, Villeurbanne, France.
Anne-Lise Bienvenu *Univ Lyon, Malaria Research Unit, SMITh, ICBMS, UMR 5246 CNRS-INSA-CPE-University Lyon1, 69622, Villeurbanne, France.
Stephane Picot *Univ Lyon, Malaria Research Unit, SMITh, ICBMS, UMR 5246 CNRS-INSA-CPE-University Lyon1, 69622, Villeurbanne, France. stephane.picot@univ-lyon1.fr.
Hospices Civils de Lyon · FRAptar (France) · FRInstitut National des Sciences Appliquées de Lyon · FRUniversité Claude Bernard Lyon 1 · FRCentre National de la Recherche Scientifique · FRÉcole d'Ingénieurs en Chimie et Sciences du Numérique · FRHôpital Femme Mère Enfant · FRInstitut Mondor de Recherche Biomédicale · FR

Funding

Annual Grant from University Lyon & CNRS 2017-2022EDCTP II- WANECAM 2 RIA2017T-2018Internship Hospices Civils de Lyon 2017-2021MORA scholarship, Republic of Indonesia 2815/DJ.I/DT.I.III/PP.04/07/2018
6 · The paper itself

Abstract

backgroundMalaria still kills young children in rural endemic areas because early treatment is not available. Thus, the World Health Organization recommends the administration of artesunate suppositories as pre-referral treatment before transportation to the hospital in case of severe symptoms with an unavailable parenteral and oral treatment. However, negative cultural perception of the rectal route, and limited access to artesunate suppositories, could limit the use of artesunate suppositories. There is, therefore, a need for an alternative route for malaria pre-referral treatment. The aim of this study was to assess the potential of intranasal route for malaria pre-referral treatment.

methodsThe permeability of artesunate through human nasal mucosa was tested in vitro. The Transepithelial Electrical Resistance (TEER) of the nasal mucosa was followed during the permeation tests. Beside, regional deposition of artesunate powder was assessed with an unidose drug delivery device in each nostril of a nasal cast. Artesunate quantification was performed using Liquid Chromatography coupled to tandem Mass Spectrometry.

resultsThe experimental model of human nasal mucosa was successfully implemented. Using this model, artesunate powder showed a much better passage rate through human nasal mucosa than solution (26.8 ± 6.6% versus 2.1 ± 0.3%). More than half (62.3%) of the artesunate dose sprayed in the nostrils of the nasal cast was recovered in the olfactory areas (44.7 ± 8.6%) and turbinates (17.6 ± 3.3%) allowing nose-to-brain and systemic drug diffusion, respectively.

conclusionArtesunate powder showed a good permeation efficiency on human nasal mucosa. Moreover it can be efficiently sprayed in the nostrils using unidose device to reach the olfactory area leading to a fast nose-to-brain delivery as well as a systemic effect. Taken together, those results are part of the proof-of-concept for the use of intranasal artesunate as a malaria pre-referral treatment.

Indexed as

AntimalarialsArtemisininsMalaria, CerebralAdministration, IntranasalArtesunateChildChild, PreschoolHumansPowdersReferral and ConsultationSuppositoriesAntimalarialsArtemisininsArtesunatePowdersSuppositoriesArtesunateNasal castNasal mucosaNose-to-brain deliveryPre-referral treatmentSevere malaria

Identifiers

PMID36221071
PMCPMC9555123
OpenAlexW4304193740

What OpenQuestion holds

Textmetadata
LicenceCC BY
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.